Rat study sug­gests Al­ler­gan's failed an­ti­de­pres­sant ra­pastinel may work as opi­oid ad­dic­tion treat­ment

Last month, when Al­ler­gan’s $AGN once-tout­ed pipeline star ra­pastinel crashed and burned a slate of piv­otal de­pres­sion stud­ies, it looked like the ex­per­i­men­tal mod­u­la­tor of the NM­DA re­cep­tor would be shroud­ed in a cloak of in­vis­i­bil­i­ty — but re­searchers may have found a way to res­cue the ex­per­i­men­tal drug by re­pur­pos­ing it as a treat­ment for opi­oid de­pen­dence.

Ju­lia Fer­rante

In the Unit­ed States, the cri­sis of opi­oid abuse, mis­use and over­dose — from pre­scrip­tion painkillers, hero­in, and syn­thet­ic opi­oids such as fen­tanyl — has reached epi­dem­ic pro­por­tions, caus­ing 130 deaths every day, ac­cord­ing to NIH es­ti­mates. Once in with­draw­al, ad­dicts are left to cope with a myr­i­ad of symp­toms in­clud­ing anx­i­ety, ag­i­ta­tion, sleep prob­lems, mus­cle aches, run­ny nose, sweat­ing, nau­sea, vom­it­ing, di­ar­rhea and opi­oid crav­ings.

In or­der to man­age these of­ten de­bil­i­tat­ing symp­toms, with­draw­al is man­aged by sub­sti­tu­tion with a less pow­er­ful opi­oid, fol­lowed by grad­ual re­duc­tion or tran­si­tion to main­te­nance ther­a­py with FDA-ap­proved med­ica­tion-as­sist­ed treat­ment (MAT) drugs such as methadone, buprenor­phine or nal­trex­one, which can have un­pleas­ant and some­times dan­ger­ous side ef­fects and of­ten must be used for months to avoid re­lapse. Al­though the process of ta­per­ing opi­oid con­sump­tion and us­ing MAT to treat opi­oid ad­dic­tion is stan­dard-of-care, it sus­tains the brain changes that re­sult in ad­dic­tion in the first place, which can lead to re­lapse be­fore treat­ment is com­plet­ed, ac­cord­ing to re­searchers who eval­u­at­ed the use of ra­pastinel in opi­oid de­pen­dence.

The tri­al in rats test­ed the use of ra­pastinel ver­sus ke­t­a­mine — a com­mon­ly-used cat tran­quil­iz­er and par­ty drug known as Spe­cial K or Kit Kat — which has been pro­posed as an al­ter­na­tive, non-opi­oid treat­ment for opi­oid with­draw­al, but it has the po­ten­tial for abuse, in­duces a trance-like state and can cause hal­lu­ci­na­tions. In fact, J&J’s $JNJ ke­t­a­mine-based de­pres­sion drug Spra­va­to has al­ready won FDA ap­proval. Ra­pastinel binds to the same re­cep­tor as ke­t­a­mine but at a dif­fer­ent site, where it con­fers a milder ef­fect.

Cyn­thia Kuhn

The sci­en­tists first in­duced opi­oid de­pen­dence in male and fe­male ado­les­cent (be­tween 28 and 30 days old) Sprague-Daw­ley rats by in­ject­ing them with mor­phine in in­creas­ing dos­es twice a day for five days. On day six, rats were in­ject­ed with nalox­one and with­draw­al signs were quan­ti­fied. The rats were then giv­en ei­ther ke­t­a­mine in­jec­tions twice dai­ly (n=12), ra­pastinel in­jec­tions every oth­er day (n=14), or saline in­jec­tions (n=24). On day nine, when the rats were giv­en nalox­one to mea­sure with­draw­al signs, ra­pastinel-treat­ed rats ex­hib­it­ed sig­nif­i­cant­ly few­er with­draw­al signs than those treat­ed with ke­t­a­mine.

The find­ings sug­gest that treat­ment with ra­pastinel in­duced safer with­draw­al, sans any se­ri­ous side ef­fects, dur­ing the crit­i­cal first days in the ef­fort to ab­stain from opi­oid use — and the sci­en­tists hy­poth­e­sized this would lead to a de­creased risk of opi­oid re­lapse.

“Ra­pastinel re­search for opi­oid de­pen­den­cy is cur­rent­ly on­ly be­ing done in ro­dents, but if the drug con­tin­ues to have suc­cess­ful tri­als, it may en­ter clin­i­cal tri­als for use in hu­mans,” said Ju­lia Fer­rante, an un­der­grad­u­ate at Vil­lano­va Uni­ver­si­ty who con­duct­ed the re­search with Cyn­thia Kuhn, pro­fes­sor of phar­ma­col­o­gy and can­cer bi­ol­o­gy at Duke Uni­ver­si­ty.

The re­searchers are look­ing to keep test­ing ra­pastinel to in­ves­ti­gate its ef­fect on the mol­e­c­u­lar lev­el and to check whether it can re­duce the risk of re­lapse. The drug has a long way to go be­fore it cross­es the fin­ish line, but if ap­proved it would like­ly be ad­min­is­tered in­tra­venous­ly, pos­si­bly in an out­pa­tient set­ting, Fer­rante added.

A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

Endpoints News writer Nicole DeFeudis has posted a snapshot of all the companies, universities and hospital-based groups now racing through the clinic, ranking them according to their place in the pipeline as well as the latest remarks available on timelines. And we’ll keep this lineup updated right through the end of the year, as the checkered flags start to fall, possibly as early as October.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

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Bayer's Marianne De Backer with Endpoints founder John Carroll, Endpoints@JPM20 (Jeff Rumans for Endpoints News)

UP­DAT­ED: Hunt­ing a block­buster, Bay­er forges an $875M-plus M&A deal to ac­quire women’s health biotech

Bayer has dropped $425 million in cash on its latest women’s health bet, bringing a UK biotech and its non-hormonal menopause treatment into the fold.

KaNDy Therapeutics had its roots in GlaxoSmithKline, which spun out several neuroscience drugs into NeRRe Therapeutics back in 2012. Five years later the team created a new biotech to focus solely on NT-814 — which they considered “one of the few true innovations in women’s health in more than two decades.”

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Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Giovanni Caforio, Bristol Myers Squibb CEO (Christopher Goodney/Bloomberg via Getty Images)

UP­DAT­ED: Bris­tol My­ers Squibb com­mits $300 mil­lion to com­bat racial dis­par­i­ties, but de­clines to re­lease own de­mo­graph­ic da­ta

After the police killing of George Floyd, a flurry of pharma and biotech companies, executives and investors jumped out to make statements, either expressing support for Black Lives Matter and the protests or condemning systemic racism.

Now, a Big Pharma company is publicly putting some teeth behind those statements. This morning, Bristol Myers Squibb announced they would spend $300 million on a broad effort to reduce racial health disparities, and diversify both their clinical trials and their own executive team and workforce.

Martin Shkreli (AP Images)

Mar­tin Shkre­li's in­fa­mous Dara­prim falls off top 20 most ex­pen­sive drugs list

Martin Shkreli incited a national uproar five years ago when he raised the price of Daraprim by a factor of 56 essentially overnight from $13.50 to $750 per pill. Now that the “Pharma Bro’s” high-priced project has received a generic, it no longer places among the most expensive drugs in the world.

GoodRx is back with the latest update of the top 20 most expensive drugs and Daraprim’s exclusion marks the biggest change. The drug had previously ranked seventh on the list’s last iteration, which came in February before the world went into quarantine. Another of Shkreli’s former companies, Retrophin, saw its Chenodal drug place in the top 10 again.

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VBL an­nounces pos­i­tive PhI­II da­ta for ovar­i­an can­cer drug; Gene­Cen­tric part­ners with Janssen on blad­der can­cer

VBL Therapeutics announced that it is on track in a Phase III trial of its drug VB-111 (ofranergene obadenovec) to treat platinum-resistant ovarian cancer in combination with paclitaxel.

After conducting its second interim analysis, the independent Data Safety Monitoring Committee (DSMC) recommended that Israel-based VBL continue full steam ahead. The committee looked at unblinded overall survival rate, which is the primary endpoint of the study, dubbed OVAL. The first analysis evaluated CA-125 response.

FDA ac­cepts pri­or­i­ty re­view for Re­gen­eron's evinacum­ab, which could join Pralu­ent in cho­les­terol mar­ket

Almost a year ago to the day, Regeneron announced solid Phase III testing results for evinacumab, a compound that’s designed to lower LDL cholesterol in patients who need treatment beyond a PCSK9 inhibitor. As that anniversary approaches, the biotech is potentially one step closer to putting it on the market.

The FDA has granted priority review and accepted a BLA for evinacumab as a supplement to other lipid-lowering therapies in individuals with homozygous familial hypercholesterolemia, Regeneron announced Wednesday morning. Regeneron’s target action date is next February 11.